Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniPathway vocabulary mapping
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
Identification of a family of human F-box proteins.
Diversity in tissue expression, substrate binding, and SCF complex formation for a lectin family of ubiquitin ligases.
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FBXO6 is a member of the FBA lectin family whose conserved G/FBA domain binds high-mannose, complex and sulfated glycans (chitobiose core essential); a Y241/W242 hydrophobic pocket is required for glycan binding, and FBXO6 co-precipitates SCF components (SKP1, CUL1, RBX1). F-box proteins have no intrinsic catalytic activity.
The F box protein Fbx6 regulates Chk1 stability and cellular sensitivity to replication stress.
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FBXO6 (Fbx6) is the substrate-recognition subunit of an SCF (SKP1-CUL1-FBXO6) E3 ligase that, via its FBA domain, binds activated CHK1 and mediates CHK1 ubiquitination and degradation to terminate the replication checkpoint; FBXO6 is mainly cytoplasmic and its level inversely correlates with CHK1 and modulates camptothecin sensitivity.
FBXW7-mediated degradation of CCDC6 is impaired by ATM during DNA damage response in lung cancer cells.
A High-Density Map for Navigating the Human Polycomb Complexome.
Architecture of the human interactome defines protein communities and disease networks.
A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape.
A reference map of the human binary protein interactome.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
The SCF Complex Is Essential to Maintain Genome and Chromosome Stability.
Multimodal cell maps as a foundation for structural and functional genomics.
AcM-UBE2M transfers NEDD8 to CRL1 E3 ubiquitin ligase complex
NEDD8:AcM-UBE2M binds CRL1 E3 ubiquitin ligase complex
CAND1 binds cytosolic CRL E3 ubiquitin ligases
COMMDs displace CAND1 from cytosolic CRL E3 ubiquitin ligase complexes
COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes
MyrG-DCUN1D3 binds CRL1 E3 ubiquitin ligase complex
Transfer of Ub from E2 to substrate and release of E2
Release of E3 from polyubiquitinated substrate
Polyubiquitination of substrate
Interaction of E3 with substrate and E2-Ub complex
Falcon deep research report for human FBXO6
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FBXO6 (FBS2) is the substrate-recognition module of an SCF-type (SCF^FBS2 / SCF^FBXO6) ubiquitin ligase that ubiquitinates N-glycoprotein substrates in protein quality control.
"FBXO6 (FBS2) is discussed as an F-box protein that serves as the substrate-recognition module of an SCF-type ubiquitin ligase (**SCF^FBS2 / SCF^FBXO6**), enabling ubiquitination of selected substrates, including **N-glycoproteins** involved in protein quality control."
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In the NGLY1/ERAD axis, SCF^FBS2 ubiquitinates ERAD glycoprotein substrates including the transcription factor NFE2L1/NRF1, which are then degraded by the proteasome after deglycosylation by NGLY1.
"ERAD glycoprotein substrates (including the transcription factor **NFE2L1/NRF1**) are ubiquitinated by multiple E3 ligases, including **SCF^FBS2**, and then degraded by the proteasome; in typical conditions, many ubiquitinated glycoproteins are thought to be **deglycosylated by NGLY1 during proteasomal degradation**."
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When NGLY1 is absent, SCF^FBS2-mediated ubiquitination of NFE2L1 impairs its processing/nuclear function and blocks induction of proteasome subunits (the proteasome bounce-back response), contributing to proteasome dysfunction.
"in the **absence of NGLY1**, SCF^FBS2-mediated ubiquitination of NFE2L1 is linked to impaired NFE2L1 processing/nuclear function and failure to induce proteasome subunits, contributing to chronic proteasome compromise and cytotoxicity."
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SCF^FBS2 acts in the cytosolic/proteasomal arm of ERAD after retrotranslocation; ubiquitinated N-glycoproteins accumulate in the cytosol when NGLY1 is absent.
"The mechanistic model places SCF^FBS2 activity in the **cytosolic/proteasomal degradation pathway for ERAD substrates** (i.e., after retrotranslocation from the ER lumen), and describes **accumulation of SCF^FBS2-ubiquitinated N-glycoproteins in the cytosol** when NGLY1 is absent."
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Genetic reduction of Fbs2/FBXO6 partially rescues Ngly1-knockout lethality in mice, and Fbs2-knockout mice are otherwise healthy, motivating FBS2 inhibition as a therapeutic concept for NGLY1 deficiency.
"genetic reduction of FBS2/FBXO6** can partially rescue lethality/phenotypes associated with **Ngly1 knockout**, and that **Fbs2 knockout mice are reported as healthy** in that review context."